The mechanism of granulocyte depletion in a patient with systemic lupus erythematosus and neutropenia was investigated. Neutrophil kinetic studies showed a shortened intravascular survival (t1/2 of 1.6 hours) in the face of an increased marrow neutrophil pool. IgG bound to the patient's neutrophils, measured by the Fab anti‐F(ab)2 assay, was nearly three times normal. The IgG neutrophil‐binding activity of the patient's serum was elevated in serial samples obtained over two years. In addition, his serum was able to opsonize normal neutrophils for ingestion by other neutrophils as detected by 14C‐1‐glucose oxidation. Enhanced IgG PMN‐binding activity was observed with sucrose density gradient fractions of the patient's serum containing either large complexes (19S or greater in size), intermediate complexes (between 7S and 19S), or monomeric IgG. Only the monomeric IgG fraction from the patient's serum, however, opsonized normal neutrophils for ingestion by other neutrophils. These results support the hypothesis that anti‐cell antibodies were responsible for the neutropenia in this patient by opsonizing neutrophils for ingestion by other phagocytic cells.

Cultures of a cell line derived from a murine mammary carcinoma that induces hypercalcemia were examined for soluble products that could induce osteoclasts to differentiate from murine bone marrow cells. The serum-free culture supernatant of this cell line stimulated growth of colonies from bone marrow cells that exhibited tartrateresistant acid phosphatase (TRAPase) activity. These TRAP-ase-positive cells demonstrated essential features of osteoclasts when cocultured with mineralized bone or dentin. The culture period required for colony development and the frequency of colony-fong cells indicated that relatively primitive marrow progenitors were stimulated by a tumor-derived factor(s) to form immature osteoclasts. Other colony-stimulating factors (CSFs), including granulocyte CSF, macrophage CSF, granulocyte-macrophage CSF and interleukin 3, were ruled out as the source of the activity produced by the tumor cells. The biological activity was successfully purified by gel fitration chromatography and reverse-phase HPLC. By SDS/PAGE,

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The Flt3 receptor is expressed in primitive hematopoietic cells and its ligand exerts proliferative effects on these cells in vitro in synergy with other cytokines. To expand on the functional properties of Flt3 ligand (FL) in vivo we treated nonhuman primates with FL and tested its ability to mobilize stem/progenitor cells when given alone or in combination with granulocyte colony-stimulating factor (G-CSF ) treatment. FL alone (200 μg/kg/day) mobilizes progenitors with slow kinetics and with a peak effect at the end of 2 weeks of treatment. The spectrum of mobilized progenitors includes myeloid, lymphoid, megakaryocytic, and osteoclastogenic but a low proportion of burst-forming unit (BFU)e. Bone marrow (BM) studies before and during the treatment suggested that proliferative effects in BM may have preceded effects on peripheral blood mobilization. To assess the synergy of FL with G-CSF in mobilization of progenitors we used two schemes: one in which G-CSF was used for the last 5 days of a 12-day treatment with FL; the other in which both cytokines were given concurrently for 5 days only (FL, 200 μg/kg; G-CSF, 100 μg/kg). Both schemes yielded much higher progenitor mobilization levels (peak levels of colony-forming cells [CFSs] 41,000 to 95,000/mL blood) than observed with either FL (CFC 4,600 to 7,300/mL) or G-CSF (8,405 ± 3,024/mL) used alone at the same doses. Furthermore, there was a progressive and significant expansion of progenitors in vitro during 2 weeks in suspension cultures of mononuclear cells or of CD34+ cells only in the animal with the combined treatment. Likewise, substantial mobilization of osteoclastogenic progenitors was documented only with the combined treatment. Given the functional properties of FL, its synergistic mobilization with G-CSF, and its anticipated good tolerance (because of the absence of an effect on mast cell activation), a clinical use is projected for this cytokine in peripheral blood transplantation settings, as well as in experiments with ex vivo gene transfer.